The primary goal ofthis initiative is to address and hopefully reduce the high, and ominously increasing, cancer mortality rates among American Indians (Als) in western South Dakota, which is 30% higher as compared to that ofthe overall US population. The specific aims ofthis project are: (1) to utilize a comprehensive model of patient navigation (PN) services to improve the following cancer-related health outcomes in our target population: to increase cancer screening rates; to decrease delays between abnormal finding, cancer diagnosis and initiation of cancer treatment, to decrease the average stage at which cancer presents, to increase cancer survival rates, and to increase access to palliative care and other services to manage the complex disease states of our clients. Evaluation of these efforts will employ a utilization -focused methodology to document progress and guide future efforts. (2) to further expand the scope of chnical cancer trials and to enroll more AI patients, as well as all medically underserved patients in our rural area, to NCI sponsored clinical trials for the more common cancer disease sites. In addition to participation in Cooperative Group trials (e.g. NCCTG, RTOG, GOG), Investigator initiated trials such as IMRT and brachytherapy studies will be opened. Participation in the Wisconsin Oncology Network (WON) will also be initiated to broaden the availability of studies for the more common tumors that are seen in this area. (3) to expand the scope of current translational research to include radiogenomics that will allow investigating the genetic risk profiles specifically related to radiation induced toxicities among AI patients by identifying genes through DNA microarrays that might predict response to treatment and ultimately guide therapy. This would include comparing lymphocytic genetic responses to irradiation from patients who had adverse reactions following irradiation to those who have not. A genetic signature could then be developed that would identify susceptible patients prior to radiation therapy.